Drug delivery device and methods having a drug cartridge

ABSTRACT

Various embodiments of a device, a kit and method for delivering a drug depot are disclosed. The device comprises a housing including a lower body, an upper body, a ring member; and a drug cartridge. The lower body defines a lower body channel. The upper body defines an upper body channel. The drug cartridge defines a depot channel. The ring member is disposed extending upward from an annular step surface of the lower body toward a housing upper end. The ring member includes indicia indicating a characteristic of one or more drug depots in the drug cartridge. A plunger has a push rod for expelling the drug depot through the cannula to a site in the patient. A kit comprises the above components. A method includes assembling the components including selecting a ring member having indicia corresponding to one or more drug depots in the drug cartridge.

BACKGROUND

Drugs may be delivered to patients by a variety of methods includingoral, intravenous, intramuscular, inhalation, topical, subcutaneousdelivery or delivery directly or locally to the treatment site (e.g.,intrathecally, intraspinally, intraarticularly, etc.). The method ofdelivery chosen depends, among other things, upon the condition beingtreated, desired therapeutic concentration of the drug to be achieved inthe patient and the duration of drug concentration that must bemaintained.

Recently, drug depots have been developed which allow a drug to beintroduced or administered to sites beneath the skin of a patient sothat the drug is slowly released over a long period of time. Such drugdepots allow the drug to be released from the depot in a relativelyuniform dose over weeks, months or even years. This method ofadministering drugs is becoming especially important and popular inmodulating the immune, inflammation and/or pain responses in treatmentof chronic conditions including rheumatoid arthritis, osteoarthritis,sciatica, carpal tunnel syndrome, lower back pain, lower extremity pain,upper extremity pain, cancer, tissue pain and pain associated withinjury or repair of cervical, thoracic, and/or lumbar vertebrae orintervertebral discs, rotator cuff, articular joint, TMJ, tendons,ligaments, muscles, and the like.

Previously, drug depots and other types of implants have been insertedinto the treatment site beneath the skin by use of a trocar device,which is a two-piece device that includes a cannula and an obdurator.The trocar device requires an incision to be made through the skin atthe site of implant of the drug depot using a separate instrument (e.g.,scalpel). A cannula and obdurator are inserted together through the skinat the incision site. Next, the obdurator is withdrawn, leaving thecannula in place as a guide for inserting the drug depot. The drug depotis inserted through the cannula, and the obdurator is used to push theimplant to the end of the cannula. The cannula and obdurator are thenwithdrawn completely, leaving the implant in place beneath the skin.

Typically, trocar devices are used to implant drug depots subcutaneouslyover a large area (e.g., 2-2.5 inches), with a typical drug depot in theorder of 1½ inches long. Thus, the trocar device is not suitable formany treatment sites because it lacks precision and may cause additionaltrauma to the tissue surrounding the site of implant.

Other drug delivery devices have been developed to simplify implantingthe drug depots. These devices have a handle for one-handed implantationof the drug depot, a needle containing the drug depot to be implantedand a rod positioned within the needle for pushing the drug depot out ofthe needle. Once the needle containing the drug depot has been insertedat the site of implant, a spring loaded trigger on the handle isactivated which causes the needle to be automatically withdrawn by aspring leaving the implanted drug depot in place. Unfortunately, it isnot possible to control the motion of the needle in these devicesbecause the needle will automatically retract upon activation of thetrigger. The complex spring loaded propelling system and trigger ofthese devices increase the chances that the device will jam and fail toeject the drug depot when required.

Conventional needle and syringe devices have been used to implant a drugdepot to sites such as, for example, the epidural space. These devicestypically utilize a syringe preloaded with the drug depot and anepidural needle. The needle is inserted through the skin, supraspinusligament, intraspinus ligament, ligamentum flavum and then into theepidural space. The drug depot is delivered through the needle to theepidural space using the syringe plunger. Conventional needle andsyringe devices often do not easily allow controlled and precisionimplant of the drug depot. If multiple drug depot implants are needed,these conventional needle and syringe devices often do not allowaccurate placement of the implant in a manner so that one drug depotdoes not substantially interfere with the dissolution of the other.

In certain methods of drug depot implantation, the drug depots aresecured in the drug cartridge by use of a bulking agent. The bulkingagent may be added to the drug depot to ensure the drug depot is securewithin the chamber, such that the drug depot is released when a plungeris engaged to dislodge the drug depot from the cartridge. The bulkingagent is sometimes added to the drug chamber before the drug depot isadded to the chamber. Other times the drug depot is added to the drugchamber first and then the drug depot is added to the chamber. Use of abulking agent to retain the drug depot in a drug cartridge requiresadditional steps and is time consuming. Thus, a drug delivery devicewhich reduces a need for use of bulking agents is needed.

New drug delivery devices are needed, which can easily allow accurateand precise implantation of a drug depot with minimal physical andpsychological trauma to a patient. When implanting several drug depots,a drug delivery device is needed that accurately and precisely allowsplacement of the drug depot in a manner such that one depot does notsubstantially interfere with the dissolution of the others.

SUMMARY

New drug delivery devices, which can easily allow accurate and preciseimplantation of a drug depot with minimal physical and psychologicaltrauma to a patient are provided.

Briefly stated, provided are embodiments of a device, a kit and methodfor delivering a drug depot are disclosed. The device comprises ahousing including a lower body, an upper body, a ring member; and a drugcartridge. The lower body defines a lower body channel. The upper bodydefines an upper body channel. The drug cartridge defines a depotchannel. The ring member is disposed extending upward from an annularstep surface of the lower body toward a housing upper end. The ringmember includes indicia indicating a characteristic of one or more drugdepots in the drug cartridge. A plunger has a push rod for expelling thedrug depot through the cannula to a site in the patient. A kit comprisesthe above components. A method includes assembling the componentsincluding selecting a ring member having indicia corresponding to one ormore drug depots in the drug cartridge.

The present disclosure provides a drug delivery device, in variousembodiments, for delivering a drug depot to a site beneath the skin ofpatient via a cannula having a proximal end and a distal end, theproximal end of the cannula having an opening to receive the drug depot,the distal end of the cannula being configured for insertion to the sitebeneath the skin of the patient and having an opening for passage of thedrug depot. The device comprises a housing including a lower body, anupper body, a ring member; and a drug cartridge, the housing having ahousing upper end, a housing lower end and a longitudinal directiondefined as extending from the housing upper end to the housing lowerend. The lower body has a lower body bottom end, a lower body upper end,and an annular step surface extending inward from an outer periphery ofthe lower body, and the lower body defines a lower body channelextending in the longitudinal direction. The lower body channel has alower body channel first end open to the lower body upper end and alower body channel second end open to the lower body bottom end. Thelower body bottom end has a coupling configuration for engaging theproximal end of the cannula. The upper body has an upper body top endand an upper body bottom end, the upper body defines an upper bodychannel open to the upper body top end, and the upper body is connectedto the lower body. The drug cartridge defines a depot channel alignedwith the lower body channel and the upper body channel, and configuredto slidably accept the drug depot. The ring member has a ring top endand a ring bottom end, and the ring member is disposed so as to extendupward from the annular step surface toward the housing upper end and soas to contact at least one of the upper body and the lower body. Aplunger has a push rod slidably receivable in the upper body channel,the depot channel, the lower body channel, and the cannula. The push rodhas a push rod end to contact the drug depot when disposed in the drugcartridge and, upon application of force, expel the drug depot throughthe cannula to the site beneath the skin of the patient.

In one embodiment of the present disclosure, there is provided a kit forpreparing a device for delivering a drug depot to a site beneath theskin of a patient in conjunction with a cannula having a proximal endand a distal end, the proximal end of the cannula having an opening toreceive the drug depot, the distal end of the cannula being configuredfor insertion to the site beneath the skin of the patient and having anopening for passage of the drug depot. The kit comprises components fora housing including a lower body, an upper body, a ring member; and adrug cartridge, the housing when assembled having a housing upper end, ahousing lower end and a longitudinal direction defined as extending fromthe housing upper end to the housing lower end. The lower body has alower body bottom end, a lower body upper end, and an annular stepsurface extending inward from an outer periphery of the lower body, andthe lower body defines a lower body channel extending in thelongitudinal direction. The lower body channel has a lower body channelfirst end open to the lower body upper end and a lower body channelsecond end open to the lower body bottom end. The lower body bottom endhas a coupling configuration for engaging the proximal end of thecannula. The upper body has an upper body top end and an upper bodybottom end, the upper body defines an upper body channel open to theupper body top end, and the upper body is connectable by snap catches tothe lower body. The drug cartridge defines a depot channel alignablewith the lower body channel and the upper body channel when installed inthe lower body, and the depot channel is configured to slidably acceptthe drug depot. The ring member has a ring top end and a ring bottomend, and the ring member is disposable so as to extend upward from theannular step surface toward the housing upper end and so as to contactat least one of the upper body and the lower body when assembled withthe upper body and the lower body. A plunger has a push rod slidablyreceivable in the upper body channel, the depot channel, the lower bodychannel, and the cannula, and the push rod has a push rod end to contactthe drug depot when disposed in the drug cartridge and, upon applicationof force, expel the drug depot through the cannula to the site beneaththe skin of the patient.

In another embodiment, a method of preparing a device to deliver a drugdepot to a target site beneath the skin is provided. The methodcomprises providing the kit described above including more than one drugdepots and more than one ring member, each having indicia. Selecting oneor more of the drug depots. Selecting one of the rings members havingindicia corresponding to the selected one or more of the drug depots.Sliding the selected ring member onto one of the upper body or the lowerbody. Installing the upper body and the drug cartridge to the lower bodyincluding engaging the upper body to the lower body using the snapcatches. Loading the drug cartridge with the selected one or more drugdepots and engaging the cannula with the lower body.

Additional features and advantages of various embodiments will be setforth in part in the description that follows, and in part will beapparent from the description, or may be learned by practice of variousembodiments. The objectives and other advantages of various embodimentswill be realized and attained by means of the elements and combinationsparticularly pointed out in the description and appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

In part, other aspects, features, benefits and advantages of theembodiments will be apparent with regard to the following description,appended claims and accompanying drawings where:

FIG. 1 a is a front elevation view of a first embodiment of a drugdelivery device of the present disclosure;

FIG. 1 b is front, left side and top perspective view of the firstembodiment of FIG. 1 a;

FIG. 1 c is a front elevation view of a plunger of the embodiment ofFIG. 1 a;

FIG. 1 d is a front elevation view of a housing of the embodiment ofFIG. 1 a:

FIG. 1 e is a left side elevation view of a housing of the embodiment ofFIG. 1 a:

FIG. 2 a is an exploded front, right side, top perspective view of thehousing of FIG. 1 e;

FIG. 2 b is a cross-sectional view of the housing of FIG. 1 d;

FIG. 3 a is an exploded front, right side, top perspective view of ahousing of a second embodiment of the drug delivery device of thepresent disclosure;

FIG. 3 b is a cross-sectional view of the housing of FIG. 3 a in anassembled state;

FIG. 3 c is an exploded perspective view of a drug cartridge of theembodiment of FIG. 3 a;

FIG. 4 a is an exploded front, right side, and bottom perspective viewof a third embodiment of a drug delivery device of the presentdisclosure;

FIG. 4 b is an exploded front, right side, and bottom perspective viewof the third embodiment of a drug delivery device of the presentdisclosure showing embodiments of a drug cartridge, funnel body, andring member in an assembled state;

FIG. 4 c is an exploded front, right side, and bottom perspective viewof the third embodiment of a drug delivery device of the presentdisclosure showing the assembly of the embodiment of a drug cartridge,funnel body, and ring member assembled together with an embodiment of ahousing body of the third embodiment;

FIG. 4 d is a cross-sectional view of a portion of the housing of FIG. 4c with the drug cartridge of FIG. 4 c installed;

FIG. 4 e is a front, right side, and top perspective view of anassembled housing of the third embodiment of a drug delivery device ofthe present disclosure;

FIG. 5 a is a front, right side, and bottom perspective view of a funnelbody having an integral second drug cartridge plate of the thirdembodiment of a drug delivery device of the present disclosure;

FIG. 5 b is a cross-sectional view of the funnel body of FIG. 5 a;

FIG. 5 c is a front, right side, and bottom perspective view of a firstdrug cartridge plate of the third embodiment of a drug delivery deviceof the present disclosure;

FIG. 5 d is a back side, right side, and bottom perspective view of thefirst drug cartridge plate of FIG. 5 c;

FIG. 6 a is a right side elevation view of a housing body of the thirdembodiment of a drug delivery device of the present disclosure;

FIG. 6 b is a front side, left side, and top perspective view of thehousing body of FIG. 6 a;

FIG. 6 c is a cross-sectional view of the housing body of FIG. 6 a takenalong a longitudinal direction of the housing body;

FIG. 6 d is a cross-sectional view of the housing body of FIG. 6 a takenalong a lateral direction of the housing body;

FIG. 7 a is a cross-sectional perspective view of the assembled housingof the third embodiment of a drug delivery device of the presentdisclosure;

FIG. 7 b is a cross-sectional view of the assembled housing of the thirdembodiment of a drug delivery device of the present disclosure;

FIG. 8 a is an exploded partial front, right side, and top sideperspective view of the housing of a fourth embodiment of a drugdelivery device of the present disclosure;

FIG. 8 b is a front side, right side, and top side perspective view ofthe housing of FIG. 8 a in an assembled state;

FIG. 8 c is a cross-sectional partial view of the assembled housing ofFIG. 8 b;

FIG. 8 d is a right side, front side, and top side perspective view ofthe housing of FIG. 8 a in an assembled state showing indicia; and

FIG. 8 e is a front side, right side, and top side perspective view ofthe housing of FIG. 8 a in an assembled state showing indicia.

It is to be understood that the figures are not drawn to scale. Further,the relation between objects in a figure may not be to scale, and may infact have a reverse relationship as to size. The figures are intended tobring understanding and clarity to the structure of each object shown,and thus, some features may be exaggerated in order to illustrate aspecific feature of a structure.

DETAILED DESCRIPTION

For the purposes of this specification and appended claims, unlessotherwise indicated, all numbers expressing quantities of ingredients,percentages or proportions of materials, reaction conditions, and othernumerical values used in the specification and claims, are to beunderstood as being modified in all instances by the term “about.”Accordingly, unless indicated to the contrary, the numerical parametersset forth in the following specification and attached claims areapproximations that may vary depending upon the desired propertiessought to be obtained by the embodiments of the present disclosure. Atthe very least, and not as an attempt to limit the application of thedoctrine of equivalents to the scope of the claims, each numericalparameter should at least be construed in light of the number ofreported significant digits and by applying ordinary roundingtechniques.

Notwithstanding that the numerical ranges and parameters setting forththe broad scope of the invention are approximations, the numericalvalues set forth in the specific examples are reported as precisely aspossible. Any numerical value, however, inherently contains certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements. Moreover, all ranges disclosed hereinare to be understood to encompass any and all subranges subsumedtherein. For example, a range of “1 to 10” includes any and allsubranges between (and including) the minimum value of 1 and the maximumvalue of 10, that is, any and all subranges having a minimum value ofequal to or greater than 1 and a maximum value of equal to or less than10, e.g., 5.5 to 10.

It is noted that, as used in this specification and the appended claims,the singular forms “a,” “an,” and “the,” include plural referents unlessexpressly and unequivocally limited to one referent. Thus, for example,reference to “a drug depot” includes one, two, three or more drugdepots.

Reference will now be made in detail to various embodiments of thepresent disclosure, examples of which are illustrated in theaccompanying drawings. While the embodiments of the present disclosurewill be described in conjunction with the illustrated embodiments, itwill be understood that they are not intended to limit the invention tothose embodiments. On the contrary, the invention is intended to coverall alternatives, modifications, and equivalents, which may be includedwithin the invention as defined by the appended claims.

The headings below are not meant to limit the disclosure in any way;embodiments under any one heading may be used in conjunction withembodiments under any other heading.

New drug delivery devices, which can easily allow the accurate andprecise implantation of multiple drug depots with minimal physical andpsychological trauma to a patient are provided. In various embodimentsthe drug delivery device allows the user to dispense multiple drugdepots, in sequence, to a site beneath the skin of the patient.

An optional feature of the drug delivery device of the presentdisclosure is that it allows the user to dispense multiple doses of thedrug in sequence.

Another optional feature is that various embodiment include occludingdevices that prevent drug depots from inadvertently being dislodged fromthe drug delivery device.

Still another feature optionally provided in various embodiments is aviewing aperture permitting visual confirmation of a number and type ofdrug depots after loading of the drug depots into the drug deliverydevice.

Yet another optional feature of various embodiments of the drug deliverydevice is a funnel body facilitating loading of small drug depots whichare difficult to manually manipulate into small apertures.

A further optional feature of various embodiments of the drug deliverydevice is an indicia ring which includes either or both of alphanumericlabeling or color coding to facilitate selection of a drug deliverydevice containing the correct drug.

A further optional feature of various embodiments of the drug deliverydevice is a method wherein the drug cartridge is loaded with drug depotsduring assembly of the device.

A further optional feature of various embodiments of the drug deliverydevice is a method wherein the drug cartridge is breach loaded with drugdepots after assembly of the device.

A further optional feature of various embodiments of the drug deliverydevice is a snap catch engagement of an upper body to a lower body so asto secure a ring member having indicia corresponding to drug depot in adrug cartridge of the device or to be breach loaded into the drugcartridge.

First Embodiment

Referring to FIGS. 1 a-1 e, a first embodiment of a drug delivery deviceof the present disclosure is shown comprising a housing 100, a cannula110, and a plunger 120. The plunger has a knob 122 with an optionalraised surface pattern 123 and a push rod 124. The raised surfacepattern provides for tactile grip of the knob 122. The illustrated raisesurface pattern is merely exemplary, and various modified patterns maybe used. The housing 100 comprises a housing body 104 and a funnel body102.

The housing body 104 optionally defines a viewing aperture 106configured to allow viewing of a drug cartridge (discussed below) withinthe housing body 104 so as to confirm presence of drug depots. Theviewing aperture 106 is sized to permit viewing of multiple drug depotsloaded into the drug cartridge.

In various embodiments of the drug delivery device the cannula 110 has aproximal end engaged to the housing via a coupling device which isoptionally embodied as, inter alia, a luer lock, threading fitting,friction fit fitting, or another fitting mechanism allowing the cannula110 to functionally couple to the housing 100 so as to permit passage ofa drug depot through the cannula 110 via entry at the proximal end andexit at a distal end. In various embodiments, the cannula 110 is hollowhaving a sufficient diameter to allow passage of the drug depot and thepush rod 124 that facilitates delivery of the drug to the designatedsite beneath the skin. The distal end of the cannula 110 is capable ofinsertion to a site beneath the skin. The size of the cannula isdictated by the procedure.

Referring to FIGS. 2 a and 2 b, internal construction of the housing 100is shown along with an embodiment of a first drug cartridge 130. Thefirst drug cartridge 130 is shown in an exploded view in FIG. 2 a andcomprises a cartridge tube 132, and proximate and distal O-rings, 136and 134. The cartridge tube 132 is optionally dimensioned to acceptmultiple drug depots.

The first drug cartridge 130 is inserted into a receiving channel 162 ofthe housing body 104 with the proximal and distal O-rings, 136 and 134,respectively disposed at proximal and distal ends of the cartridge tube132 as shown in the cross-sectional view of FIG. 2 b. Drug depots 140are disposed in the cartridge tube 132 and retained in the cartridgetube 132 by virtue of the proximal and distal O-rings, 136 and 134,having an internal diameter which is slightly less than an externaldiameter of the drug depots 140. For the purposes of the presentdisclosure in this respect, “slightly less” is intended to an amountsmall enough that, upon force being applied to the drug depots 140 bythe push rod 124, the distal O-ring 134 will stretch radially outwarddue to force applied by the drug depots 140 to permit passage of thedrug depots 140 therethrough without damage to the integrity of the drugdepots 140. The first drug cartridge 130 is preferably formed of a clearor translucent material to permit viewing of the drug depots 140 via theviewing aperture 106 when the first drug cartridge 130 is installed inthe housing body 104 as shown in FIG. 2 b.

The funnel body 102 has a funnel bore 150 which has a funnel taper atthe proximal end and transitions to a tubular configuration 151 openingat a distal end in alignment with the proximate O-ring 136. The funnelbody 102 has a stepped configuration with a first step portion 154 and asecond stepped portion 161 which respectively fit into a stepped recessof the housing body 140 comprising a first recess opening 152 and asecond recess opening 161. The first step portion 154 has key ridges 156(one visible in FIG. 2 a with asymmetric opposing key ridge on the farside) which fit into key channels 158 defined in a wall of the firstrecess opening 152. The dimensioning of the key ridges 156 and keychannels 158 is optionally configured to provide for a press fit of thefunnel body 102 into the housing body 104. An alternative couplingmechanism for fixing the funnel body 102 to the housing body 104 may beemployed such as threading, adhesives, clips, or a cantilevered arm snapcatch as discussed below with reference to other embodiments of thepresent disclosure. The funnel bore 150 provides for ease of insertionof the push rod 124 of the plunger 120 as the funnel taper guides adistal end of the push rod 124 into the tubular configuration 151 of thefunnel bore 150 upon insertion by a user. The funnel taper also guidesdrug depots 140 into the tubular configuration 151 when the drugdelivery device is breach loaded.

The housing body 104 shown has an exemplary embodiment of the couplingdevice for connecting the cannula 110 comprising a nipple portion 174defining a nipple channel 175 which is in alignment with the distalO-ring 134 so as to permit passage of the drug depots 140 therethroughand into the cannula 110 (shown in FIG. 1 a), and a coupling bore 170with an internal thread 172 for attachment of the cannula 110 via a luerlock mechanism known in the art. As noted above, the embodiments of thepresent disclosure is not limited to such a coupling device, and it isconsidered to be within the scope and spirit of the present disclosureto modify the housing body 104 as may be required to adapt othercoupling devices.

The drug depots 140 are optionally loaded into the cartridge tube 130during assembly of the first drug cartridge 130 into the housing body104 and prior to placement of the proximate O-ring 136 and closure withthe housing 100 with the funnel body 102. Such an operation is carriedout by first installing the distal O-ring 134 into a bottom of thereceiving channel 162 followed by installing the cartridge tube 132 intothe receiving channel 162 such that a bottom of the cartridge tube 132contacts or is proximate to the distal O-ring 134. Next, one or more ofthe drug depots 140 are inserted into the cartridge tube 132 via theproximate end thereof. Following insertion of the drug depots 140, theproximate O-ring 136 is installed followed by press fitting of thefunnel body 102. Alternatively, the drug depots 140 may be breach loadedinto the first drug cartridge 130 after assembly of the housing 100including installation of the first drug cartridge 130. Using breachloading the drug depots 140 are disposed into the funnel bore 150 sothat they are guided into the tubular configuration 151 of the funnelbore 150 by the funnel taper. Once in the tubular configuration 151 thedrug depots 140 fall to the proximate O-ring 136 which restricts furtherfalling. The push rod 124 of the plunger 120 is then used to push theindividual ones of the drug depots 140 through the aperture of theproximate O-ring 136, expanding the proximate O-ring 136 in the process,and into the cartridge tube 132 whereat the drug depots 140 are retainedby the proximate and distal O-rings, 136 and 134, until use.

Administration of the drug depots 140 is effected by first engaging thecannula 110 via the coupling device of the housing body 104. As anexample without limitation in the illustrated embodiment, a luer lockcoupling is used which engages the internal thread 172 of the couplingbore. An indicator ridge 108 is optionally provided on the housing body104 such that when proper coupling of the luer lock is made, acorresponding ridge on a luer lock portion of the cannula 110 alignswith the indicator ridge 108 of the housing body 104. Prior to disposingthe drug depots 140 in the patient, the user visually confirms presenceof a correct number and type of the drug depots 140 via the viewingaperture 106 and the transparent body of the cartridge tube 132. Next,the cannula is inserted into the patient to place the tip of the cannula110 at a desired location for disposition of the drug depots 140. Thenthe push rod 124 of the plunger 120 is inserted into the funnel bore 150and on through the first drug cartridge 130, the housing body 104, andthe cannula 110, so as to push the drug depots 140 out of the cannula110 at the desired disposition location in the patient.

Second Embodiment

Referring now to FIGS. 3 a-3 c, a second embodiment of the drug deliverydevice of the present disclosure is shown, which is the same as thefirst embodiment except as related herein. Components substantiallycorresponding to those of the first embodiment, yet modified, areidentified by like reference numerals with an alphabetic characterappended thereto in order to facilitate an understanding of therelationships of the embodiments of the present disclosure. Componentswhich are the same as in prior described embodiments have the samereference designators and further description thereof is omitted unlessrequired to describe cooperation with modified components.

A second drug cartridge 180 is used in place of the first drug cartridge130 and is inserted into a second receiving channel 162 a of a secondhousing body 104 a. The second receiving channel 162 a is rectangular incross section while the first receiving channel 162 is circular. Thesecond drug cartridge 180 comprises first and second plates, 182 and184, respectively having first and second cantilever arms, 194 and 196,with corresponding ramped protrusions, 195 and 197, at distal endsthereof with proximate ends thereof acting as fixed cantilever mounts.The first and second plates, 182 and 184, each have a half channel, 190and 192, extending from an end of a respective plate along a body of therespective plate and a corresponding one of the cantilever arms, 194 and196, up to a corresponding one of the ramped protrusions, 195 and 197.Optionally, the first and second plates, 182 and 184, are formedidentically to reduce manufacturing and assembly costs. The first andsecond plates, 182 and 184, each have bosses 186 and corresponding bossreceiving holes 188. The first and second plates, 182 and 184, arefitted together as illustrated in FIG. 3 c, with bosses 186 fitting intoopposing boss receiving holes 188. Optionally, the bosses 186 and bossreceiving holes 188 are dimensioned to provide a press fit facilitatingretention of the first and second plates, 182 and 184, to each other.Alternative means of securing the first and second plates, 182 and 184,may be used such as adhesives, clips, molded snap latches, or othermeans known to those skilled in the art.

When the first and second plates, 182 and 184, are assembled together,the half channels, 190 and 192, align together and define a depotchannel 199 for receipt of the drug depots 140 as shown in FIG. 3 b. Theramped protrusions, 195 and 197, each at least partially occlude thedepot channel to an extent sufficient to prevent the drug depots 140from falling out of the second drug cartridge 180 via either one of endsof the depot channel 199. Material selection and dimensioning of thecantilever arms, 194 and 196, are sufficient to provide a springconstant allowing deflection of the cantilever arms by force of the drugdepots being urged through the funnel channel bore 150 and the depotchannel 199 by the push rod 124 of the plunger 120 without comprise ofthe integrity of the drug depots 140.

Preferably, although not required, the first and second plates, 182 and184, are formed of clear or transparent material to permit visualconfirmation of the number and type of the drug depots 140 loaded in thesecond drug cartridge 180 via the viewing aperture 106. As in the caseof the first drug cartridge 130, the drug depots 140 may be loaded intothe second drug cartridge 180 either during assembly or post assembly bybreach loading.

While in the illustrated embodiment of the second drug cartridge 180 thefirst and second plates, 182 and 184, are identical, this is not arequirement of the present disclosure. Alternatively, one of the platesmay include both of the cantilever arms, 194 and 196, while another oneof the plates defines a continuous half channel. Likewise, the bosses186 and receiving holes 188, may be redistributed among the plates withall bosses or all boss receiving holes on one plate and with allreceiving holes or all bosses on another one of the plates. Otherconfigurations of the plates may be effected which provide for theretention of the drug depots 140 such as providing an elastically biasedocclusion of a depot channel by means of elastomeric buttons, coilssprings, fuzz balls formed of plastic, elastic foam material, flexiblefibers, or biased beveled end pins, which are merely examples of otherretention devices and not considered limiting.

The drug depots 140 are optionally loaded into the second drug cartridge180 during assembly of the second drug cartridge 180 and prior toplacement of the second drug cartridge 180 into the housing body 104 aand closure with the funnel body 102. Such an operation is carried outby placement of one or more of the drug depots into the half channel 192of the second plate 184. Next, the first plate 182 is pressed into placeover the second plate 184. Then, the assembled second drug cartridge 180is installed into the receiving channel 162 a and the funnel body 102 ispressed into place. Alternatively, the drug depots 140 may be breachloaded into the second drug cartridge 180 after assembly of the housing100 including installation of the second drug cartridge 180. Usingbreach loading the drug depots 140 are disposed into the funnel bore 150so that they are guided into the tubular configuration 151 of the funnelbore 150 by the funnel taper. Once in the tubular configuration 151 thedrug depots 140 fall into the second drug cartridge 180 up to a first ofthe ramped protrusions, 195 and 197, encountered. The push rod 124 ofthe plunger 120 is then used to push the drug depots 140 past the firstof the ramped protrusions, 195 and 197, encountered, deflecting acorresponding one of the first and second cantilever arms, 194 and 196,in the process, to permit passage of the drug depot into the depotchannel formed by the first and second half channels, 190 and 192, to aposition between the first and second ramped protrusion, 195 and 197.The drug depots 140 are retained until use in the second drug cartridge180 by the first and second ramped protrusions, 195 and 197, occludingthe depot channel.

Administration of the drug depots 140 is effected by first engaging thecannula 110 via the coupling device of the housing body 104 a and thecannula 110, as in the example of the first embodiment, a luer lockcoupling is used which engages the internal thread 172 of the couplingbore. An indicator ridge 108 is provided on the housing body 104 suchthat when proper coupling of the luer lock is made, a correspondingridge on a luer lock portion of the cannula 110 aligns with theindicator ridge of 108 of housing body. Prior to disposing the drugdepots 140 in the patient, the user visually confirms presence of acorrect number and type of the drug depots 140 via the viewing aperture106 and the transparent body of the second drug cartridge 180. Next, thecannula 110 is inserted into the patient to place the tip of the cannula110 at a desired location for disposition of the drug depots 140. Thenthe push rod 124 of the plunger 120 is inserted into the funnel bore 150and on through the second drug cartridge 180, the housing body 104 a,and the cannula 110, so as to push the drug depots 140 out of thecannula 110 at the desired disposition location in the patient.

Third Embodiment

Referring now to FIGS. 4 a-4 e, a third embodiment of the of the drugdelivery device of the present disclosure having a partially integrateddrug cartridge and a ring member is shown which is the same as priordescribed embodiments except as related herein. Components substantiallycorresponding to those of the second embodiment, yet modified, areidentified by like reference numerals with an alphabetic characterappended thereto in order to facilitate an understanding of therelationships of the embodiments of the present disclosure. Componentswhich are the same as in prior described embodiments have the samereference designators and further description thereof is omitted unlessrequired to describe cooperation with modified components.

In FIG. 4 a an exploded view of the third embodiment of the presentdisclosure is shown wherein a third housing body 104 b is configured toaccept installation of a first ring member 210, and a second funnel body102 b having the partially integral drug cartridge comprised of firstcartridge plate 200 and second cartridge plate 202. The second cartridgeplate 202 is formed integrally with a funnel portion of the secondfunnel body 102 b. The first cartridge plate 200 snaps onto the secondcartridge plate 202 by means of cantilever catch hook arms 208 engaginga distal end of the first cartridge plate 200, as shown in FIG. 4 d,while a proximate end of the first cartridge plate 200 is engaged withhinging apertures 204 of the second funnel body 102 b. Assembly of thethird embodiment is accomplished by snapping the first cartridge plate200 onto the second cartridge plate 202, sliding the first ring member210 to engage an upper portion of the second funnel body as shown inFIG. 4 b, followed by sliding the second funnel body 102 b intoengagement with the third housing body 104 b thereby completing assemblyof a third housing 100 c as shown in FIGS. 4 c and 4 e.

As illustrated in FIG. 4 e, the first ring member 210 has a bottom edgecontacting a top ledge 254 of the third housing body 104 b and has a topedge extending to an end of the third housing 100 c and surrounding theupper portion of the second funnel body 102 b. surrounding the upperportion of the funnel body 102 b renders tapering with the assembledthird housing 104 b difficult because disassembly requires that thesecond funnel body 102 b be forcibly separated from the housing body 104c and a lack of an exposed periphery of the second funnel body 102 binhibits an ability of one to firmly grasp the second funnel body 102 b.

When the plunger 120 is fully inserted, the plunger knob 122 is adjacentthe first ring member 210. Optional selection of different colors forthe plunger knob 122 and the first ring member 210 provides contrastwhen the plunger 120 is fully inserted facilitating visual confirmationthat the plunger 120 is fully inserted.

Referring to FIGS. 5 a and 5 b, the second funnel body 102 b has thesecond cartridge plate 202 molded integrally therewith. A thirdcantilever arm 204, having a ramped protrusion 205, is formed in thesecond cartridge plate 202 by a defining aperture in the secondcartridge plate 202. A first half depot channel 203 extends the lengthof the second cartridge plate 202, with the exception of the rampedprotrusion 205 and the defining aperture, and communicates with thetubular configuration 151 of the funnel bore 150. Cantilever catch arms220, having catch hook protrusions 221, are provided on opposing sidesof the second funnel body for engaging with the third housing body 104 bas described below.

Referring to FIGS. 5 c and 5 d, the first cartridge plate 200 has afourth cantilever arm 208, having a ramped protrusion 207, formed in thefirst cartridge plate 202 by a defining aperture. A second half depotchannel 209 extends the length of the first cartridge plate 200, withthe exception of the ramped protrusion 207 and the defining aperture,and communicates with the tubular configuration 151 of the funnel bore150. Hinging protrusions 212 are provided at a proximate end of thefirst cartridge plate 200 and are configured to engage the hingingapertures 204 of the second funnel body 202. Hook engaging protrusions214 are provided at a distal end of the first cartridge plate 200 andare configured to engage the cantilever catch hook arms 208 of thesecond cartridge plate 202. A bevel on the hook engaging protrusions 214slidably engages a bevel on the cantilever catch hook arms 208 to impartlateral force to the cantilever catch hook arms 208 to deflect thecantilever catch hook arms 208 when the first cartridge plate 200 issnapped into position on the second cartridge plate 202. It will berealized by those skilled in the art in view of this disclosure that thepositioning of the cantilever catch hook arms 208 and the hook engagingprotrusions 214 may be interchanged. Additionally, other methods may beemployed to engage the first and second cartridge plates, 200 and 202,with each other and adaptation of other engagement methods is consideredto be within the scope and spirit of the present disclosure.

As shown in FIG. 5 d, a rectangular recess 215 is provided in a side ofthe first cartridge plate 200 opposite that of the second half depotchannel 209 and the fourth cantilever arm 208. The rectangular recess215 provides for thinning of the fourth cantilever arm 208 to adjust itsspring coefficient to provide a sufficient biasing force permittingpassage of the drug depots 140 without damaging the integrity thereof,as discussed previously in relation to the second embodiment of thepresent disclosure. As in the cases of the first and second drugcartridges, 130 and 180, the drug depots may be loaded into thepartially integrated second drug cartridge either during assembly orpost assembly by breach loading.

Preferably, although not required, at least one, and more preferablyboth the first cartridge plate 200 and the second cartridge plate 202are formed of clear or transparent material to permit visualconfirmation of the number and type of the drug depots 140 loaded in thepartially integrated drug cartridge via the viewing aperture 106. As inthe case of the first and second drug cartridges, 130 and 180, the drugdepots 140 may be loaded into the second drug cartridge 180 eitherduring assembly or post assembly by breach loading.

Referring to FIGS. 6 a-6 d, an embodiment of a configuration of thethird housing body 104 b of FIGS. 4 a-4 e is shown. While similar to theembodiment of the second housing 104 a, the third housing body 104 has amating configuration for engagement of the second funnel body 102 bdifferent from the press fit engagement that the second housing body 104a has for engaging the funnel body 102. Instead, the third housing body104 b has piers 251 and stanchions 240, with each of the stanchions 240including a snap engagement aperture 242. Additionally, the thirdhousing body 104 b has buttresses 244, shown in FIG. 6 d, arranged toaccept a distal end of the integral drug cartridge of the second funnelbody 102 b instead of the second receiving channel 162 a of the secondhousing body 104 a. Alternatively, the buttresses 244 may be replacedwith solid material defining an aperture configured to accept the distalend of the integral drug cartridge as in the case of the receivingapertures 160 and 160 a of the first and second embodiments.

Referring to FIGS. 7 a and 7 b, orthogonal cross sections of the thirdembodiment of the present disclosure are shown detailing the mechanicalengagement of the third housing body 104 b, the first ring member 210,and the second funnel body 102 b having the partially integral drugcartridge. The first cartridge plate 200 is snapped into engagement withthe second cartridge plate 202 via the cantilever catch hook arms 208and the hinging protrusions 212 (not shown). The distal end of thepartially integral drug cartridge is retained in position by thebuttresses 244.

The second funnel body 102 b is secured in the third housing body 104 bby means of the cantilever catch arms 220 and the catch hook protrusions221 respectively engaging the stanchions 240 and the snap engagementapertures 242. Additionally, the second funnel body 102 b has flanges250 which seat on ends of the stanchions 240 in cooperation with theengagement of the cantilever catch arms 220 thereby securing the secondfunnel body 102 b in a longitudinal direction of the third housing body104 b. The first ring member 210 is secured in the longitudinaldirection between a ledge 254 of the third housing body 104 b andinclined faces 256 of the second funnel body 102 b, which engagecorresponding inclined faces 258 of the first ring member 210.

The drug depots 140 are optionally loaded into the partially integraldrug cartridge during assembly of the partially integral drug cartridge180 and prior to placement of the partially integral drug cartridge 180into the housing body 104 a and closure with the funnel body 102. Suchan operation is carried out by placement of one or more of the drugdepots into the half channel 192 of the second plate 184. Next, thefirst plate 182 is pressed into place over the second plate 184. Then,the assembled partially integral drug cartridge is installed into thehousing body 104 b and the funnel body 102 b is pressed into place.Alternatively, the drug depots 140 may be breach loaded into thepartially integral drug cartridge after assembly of the partiallyintegral drug cartridge and installation thereof into the housing body104 b as shown in FIGS. 7 a and 7 b. Using breach loading the drugdepots 140 are disposed into the funnel bore 150 so that they are guidedinto the tubular configuration 151 of the funnel bore 150 by the funneltaper. Once in the tubular configuration 151 the drug depots 140 fallinto the partially integral drug cartridge down to the ramped protrusion205. The push rod 124 of the plunger 120 is then used to push the drugdepots 140 past the ramped protrusion 205, deflecting the thirdcantilever arm 204 in the process to permit passage of the drug depotinto the depot channel formed by the first and second half channels, 203and 209, to a position between the ramped protrusions, 203 and 209. Thedrug depots 140 are retained until use in the partially integral drugcartridge by the ramped protrusions, 203 and 209, occluding the depotchannel.

Administration of the drug depots 140 is effected by first engaging thecannula 110 via the coupling device of the housing body 104 b and thecannula 110, as in the example of the first embodiment, a luer lockcoupling is used which engages the internal thread 172 of the couplingbore. An indicator ridge 108 is provided on the housing body 104 suchthat when proper coupling of the luer lock is made, a correspondingridge on a luer lock portion of the cannula 110 aligns with theindicator ridge of 108 of housing body. Prior to disposing the drugdepots 140 in the patient, the user visually confirms presence of acorrect number and type of the drug depots 140 via the viewing aperture106 and the transparent body of the partially integral drug cartridge.Next, the cannula 110 is inserted into the patient to place the tip ofthe cannula 110 at a desired location for disposition of the drug depots140. Then the push rod 124 of the plunger 120 is inserted into thefunnel bore 150 and on through the partially integral drug cartridge,the housing body 104 b, and the cannula 110, so as to push the drugdepots 140 out of the cannula 110 at the desired disposition location inthe patient.

Fourth Embodiment

Referring to FIGS. 8 a-8 c, a fourth embodiment of the presentdisclosure has an alternative ring member arrangement which entailsvariations of the first ring member 210, the second funnel body 102 b,and the third housing body 104 b of FIGS. 7 a and 7 b yielding a secondring member 210 c, a fourth funnel body 102 c, and a fourth housing body104 c. The fourth embodiment of the drug delivery device of the presentdisclosure is the same as prior described third embodiment except asrelated herein. In particular, the fourth embodiment provides analternative ring member configuration to the ring member configurationof the third embodiment. Components substantially corresponding to thoseof the third embodiment, yet modified, are identified by like referencenumerals with an alphabetic character appended thereto in order tofacilitate an understanding of the relationships of the embodiments ofthe present disclosure. Components which are the same as in priordescribed embodiments have the same reference designators and furtherdescription thereof is omitted unless required to describe cooperationwith modified components.

The fourth housing body 104 c has a stanchion ring 104 c defining snapengagement apertures 242 c instead of the stanchions 240 of the thirdhousing body 104 b. The second ring member 210 c lacks the inclinedfaces 258 of the first ring member 210 and instead has a wider ring endsurface 260. The fourth funnel body 102 c lacks the inclined surface 256of the third funnel body and instead has a funnel flange 262 which formsan annular end surface wider than that of the third funnel body 102 band an outer peripheral surface 266. The funnel flange 262 has a flangeunder-face 264 which secures the second ring member 210 c in thelongitudinal direction in conjunction with the ledge 254 of the fourthfunnel body 102 c. The outer peripheral surface 266 remains exposedafter assembly of the drug delivery device as shown in FIGS. 8 b, 8 d,and 8 e. The fourth funnel body 102 c has cantilever catch arms 220 cwhich merely differ from those of the third funnel body 102 b in lackinga bend at base ends thereof. As will be appreciated by those skilled inthe art having benefit of the present disclosure, snap catches orlatches, as described above, may be configured to interchange positionsof the cantilever arm and catch hook with the position of the snapengagement aperture. The loading and use of the fourth embodiment of thedrug delivery device is the same as for the third embodiment of the drugdelivery device.

Indicia Features

Each of the third and fourth embodiments of the present disclosurecomprises ring members which may be used for identification purposes.The first and second ring members, 210 and 210 c, are optionally colorcoded and/or provided with indicia, 250 and 252, indicating, for exampleand without limitation, drug type, drug name, dosage, lot no., orexpiration date. The provision of the indicia is shown in FIGS. 8 d and8 e with relation to the second ring member 210 with the understandingthat a similar indicia arrangement is also applicable to the first ringmember 210. The use of either of the first or second ring members, 210or 210 c, permits the drug delivery device to be conveniently marked attime of assembly by choosing a ring member having the required indicia.Hence, other more complex components need only be stocked in genericconfigurations lacking indicia.

Modifications of Embodiments of the Drug Delivery Device A.Incorporation of Snap Latch in First and Second Embodiment

The funnel body 102 of the first and second embodiment of the drugdelivery device does not require use of a ring member and press fitsinto the housing body 104 or 104 a. While the funnel body 102 is shownin a press fit configuration, it will be understood by those skilled inthat art that the funnel body 102 is also modifiable to incorporate thecantilever catch arms, 220 or 220 c, and the catch hook protrusions 221of the third or fourth funnel bodies, 102 b or 102 c, while modifyingthe first or second housing body, 104 or 104 a, to include thestanchions 240 or the stanchion ring 240 c and the included snapengagement apertures, 242 or 242 c.

B. Incorporation of Ring Member in First and Second Embodiment

The present disclosure further includes embodiments wherein the ringmembers, 210 or 210 c, are incorporated into either the first or secondembodiments described above. Incorporation involves reducing an outerdiameter of at least a portion of the funnel body 102 to accept the ringmember, 210 or 210, in accordance with the corresponding configurationsof the third or fourth funnel bodies, 102 b or 102 c. Alternatively, orin addition to the adjustment of the funnel body 102, a similaradjustment of the housing body 104 may also be made to accommodateeither of the ring members 210 or 210 c.

C. Incorporation of Press Fit in Third or Fourth Embodiment

The present disclosure further includes embodiments of the drug deliverydevice wherein the third or fourth embodiments of the drug deliverydevice are modified to utilize a press fit of the funnel body into thehousing body. The third and fourth embodiments detailed above utilizesnap catches to engage the funnel bodies, 102 b and 102 c, with thehousing bodies, 104 b and 104 c. In order to utilize a press fitengagement as used in the first and second embodiments, the cantilevercatch arms, 220 or 220 c, and the catch hook protrusions 221 of thesecond or third funnel bodies, 102 b or 102 c, may be replaced with aprong to engage in a press fit manner a groove or aperture in modifiedstanchions of the third or fourth housing bodies, 104 or 104 a.

D. Incorporation of First and Second Drug Cartridges into the Third orFourth Embodiments

The present disclosure further includes embodiments of the drug deliverydevice wherein the third or fourth embodiments of the drug deliverydevice, having ring members and the partially integral drug cartridge,are modified to accept either of the first or second drug cartridges,130 or 180, in place of the partially integral drug cartridge. Thecorresponding housing body, 104 b or 104 c, is modified to includeengaging portions of the first or second housing body, namely toincorporate either the receiving channel 162 for the first drugcartridge 102 or the receiving channel 162 a for the second drugcartridge 180. Similarly, the corresponding funnel body, 102 b or 102 c,is modified to eliminate the integral drug cartridge plate 202 and toextend the tubular configuration 151 of the funnel bore 150 to orproximate to the corresponding proximate end of the first or second drugcartridge 130 or 180.

E. Integral Incorporation of Drug Cartridges into the Housing

The drug delivery device of the present disclosure further includesembodiments of the first through fourth above described embodimentswherein the drug cartridge of the respective embodiments is madeintegral with the housing body. Hence, unless expressly stated otherwisein the appended claims, integration of drug cartridge structure into ahousing body is considered to be within the scope of the claims. Thus,claiming a housing body and a drug cartridge does not exclude the drugcartridge being integral with the housing body or parts thereof absentclaim language to the contrary.

In the first embodiment the housing body 104 may be formed in first andsecond housing body halves which respectively incorporate first andsecond half depot channels which replace a depot channel defined by thecartridge tube 132. Cavities are defined by each of the first and secondhousing body halves which are configure to accept the proximal anddistal O-rings 136 and 134.

In the second embodiment the housing body 104 a may be formed in firstand second housing body halves which respectively incorporate first andsecond half depot channels which replace a depot channel defined by thehalf channels of the first and second plates, 182 and 184. The first andsecond cantilever arms, 194 and 196, are optionally molded into thefirst and second housing body halves or attached by means known to thoseskilled in the art. Alternatively, the first and second cantilever arms,194 and 196, are optionally replaced with deformable devices atpositions corresponding to the first and second ramped protrusions, 195and 197, and which are accepted in cavities defined by one or both ofthe first and second housing body halves.

In the third and fourth embodiments the housing body, 104 b or 104 c,may be formed in first and second housing body halves which respectivelyincorporate first and second half depot channels which replace a depotchannel defined by the half channels of the first and second cartridgeplates, 200 and 202. The third and fourth cantilever arms, 204 and 208,are optionally molded into the first and second housing body halves orattached by means known to those skilled in the art. Alternatively, thethird and fourth cantilever arms, 204 and 208, are optionally replacedwith deformable devices at positions corresponding to the rampedprotrusions, 205 and 207, and which are accepted in cavities defined byone or both of the first and second housing body halves.

E. Adaptation for a Single Occluding Device

The drug delivery device of the present disclosure further includesembodiments of the first through fourth above described embodimentswherein one of the occluding devices is absent. In the absence of theoccluding device at the proximate end of the respective drug cartridge,a closing device may be applied to the funnel bore to prevent the drugdepot from falling out. In the absence of the occluding device at thedistal end of the respective drug cartridge, a closing device may beapplied to the nipple channel to prevent the drug depot from fallingout.

F. Modification of Cantilever Arms

The second, third and fourth embodiments of the present disclosureinclude the cantilever arms 194, 195, 204, and 208, respectively havingramped protrusions, 195, 197, 205, and 207. As shown in the figures, theprotrusions, 195, 197, 205, and 207, are configured as bumps on thecantilever arms 194, 195, 204, and 208. It is considered to be withinthe scope and spirit of the present disclosure that in place of theramped protrusions, 195, 197, 205, and 207, being distinct portions ofthe cantilever arms 194, 195, 204, and 208, the cantilever arms 194,195, 204, and 208 may extend in a continuous manner angling into thedepot channel so as to protrude sufficiently into the depot channel toprevent passage of a drug depot. As such, both the ramped protrusions,195, 197, 205, and 207, and portions of the cantilever arms 194, 195,204, and 208, modified to extend into the depot channel are consideredto be “protruding portion(s)” of the cantilever arms 194, 195, 204, and208.

Cannula

The cannula or needle of the drug delivery device is designed to causeminimal physical and psychological trauma to the patient. Cannulas orneedles include tubes that may be made from materials, such as forexample, polyurethane, polyurea, polyether(amide), PEBA, thermoplasticelastomeric olefin, copolyester, and styrenic thermoplastic elastomer,steel, aluminum, stainless steel, titanium, nitinol, metal alloys withhigh non-ferrous metal content and a low relative proportion of iron,carbon fiber, glass fiber, plastics, ceramics or combinations thereof.The cannula or needle may optionally include one or more taperedregions. In various embodiments, the cannula or needle may be beveled.The cannula or needle may also have a tip style for accurate treatmentof the patient depending on the site for implantation. Examples of tipstyles include, for example, Trephine, Cournand, Veress, Huber,Seldinger, Chiba, Francine, Bias, Crawford, deflected tips, Hustead,Lancet, or Tuohey. In various embodiments, the cannula or needle mayalso be non-coring and have a sheath covering it to avoid unwantedneedle sticks.

The cannula or needle of the drug delivery device has an internaldiameter that is larger than the diameter of at least part of the pushrod 124 (e.g., tip, middle, etc.) of the plunger 120 to allow at leastpart of the plunger to be slidably received within the cannula orneedle. In various embodiments, the diameter of the cannula or needle issubstantially the same throughout. In other embodiments, the diameter ofthe needle or cannula becomes smaller approaching the distal end fordrug delivery.

The dimensions of the hollow cannula or needle, among other things, willdepend on the site for implantation. For example, the width of theepidural space is only about 3-5 mm for the thoracic region and about5-7 mm for the lumbar region. Thus, the needle or cannula, in variousembodiments, can be designed for these specific areas. Some examples oflengths of the cannula or needle may include, but are not limited to,from about 50 to 150 mm in length, for example, about 65 mm for epiduralpediatric use, about 85 mm for a standard adult and about 150 mm for anobese adult patient. The thickness of the cannula or needle will alsodepend on the site of implantation. In various embodiments, thethickness includes, but is not limited to, from about 0.05 to about1.655. The gauge of the cannula or needle may be the widest or smallestdiameter or a diameter in between for insertion into a human or animalbody. The widest diameter is typically about 14 gauge, while thesmallest diameter is about 25 gauge. In various embodiments the gauge ofthe needle or cannula is about 17 to about 25 gauge.

In various embodiments and those described above, the plunger 120,cannula 110 or drug depot 140 include markings that indicate location ator near the site beneath the skin. Radiographic markers can be includedon the drug depot to permit the user to accurately position the depotinto the site of the patient. These radiographic markers will alsopermit the user to track movement and degradation of the depot at thesite over time. In this embodiment, the user may accurately position thedepot in the site using any of the numerous diagnostic-imagingprocedures. Such diagnostic imaging procedures include, for example,X-ray imaging or fluoroscopy. Examples of such radiographic markersinclude, but are not limited to, barium, calcium phosphate, and/or metalbeads.

In various embodiments, the needle or cannula 110 may include atransparent or translucent portion that can be visualizable byultrasound, fluoroscopy, x-ray, or other imaging techniques. In suchembodiments, the transparent or translucent portion may include aradiopaque material or ultrasound responsive topography that increasesthe contrast of the needle or cannula relative to the absence of thematerial or topography.

Cannula Coupling Device

In various embodiments of the present disclosure, including thosepresented above, surrounding the opening of the proximal end of thecannula or needle is a generally cylindrical hub having an engagementmeans for engaging the housing body. In the above embodiments thehousing bodies are shown having internal threading as part of a couplingdevice. This depiction of a portion of a coupling device is forexemplary purposes only and is not limiting. The present disclosureoptionally includes alternative coupling devices which include, but arenot limited to, threading, tracks, clips, ribs, projections, and thelike that allow a secure connection between the housing and the proximalend of the cannula. For example, in various embodiments the couplingdevice may be a luer lock connection, where the cannula has matingthreads that mate with the threads disposed on or in the housing.

Housing and Drug Cartridge Material

In various embodiments of the present disclosure, including thosepresented above, the housing is optionally formed of any of variousshapes including, but not limited to, cylindrical or round such that thehousing allows for the affixation to the cannula as well as acceptanceof the drug cartridge and the plunger. In the embodiments presentedabove, the housings of the first through fourth embodiments include atleast one side configured to prevent rolling of the housing. Asillustrated, the housings optionally have a truncated circular crosssection presenting opposing substantially flat sides which is anexemplary and non-limiting embodiment.

The housing is optionally provided with contours to allow easy graspingof the device during use for insertion of the drug depot. Furthermore,the housing is optionally angled for right and left hand users or can begeneric for both hands.

The housing and drug cartridge is optionally comprised of any of avariety of materials, such as, for example, polyurethane, polyurea,polyether(amide), PEBA, thermoplastic elastomeric olefin, copolyester,and styrenic thermoplastic elastomer, steel, aluminum, stainless steel,titanium, nitinol, metal alloys with high non-ferrous metal content anda low relative proportion of iron, carbon fiber, glass fiber, plastics,ceramics or combinations thereof.

Informative Indicia

In various embodiments of the drug delivery device of the presentdisclosure, including those presented above, the housing is optionallyprovided with indicia such dose indicator markings (e.g., numbers,lines, letters, radiographic markers, etc.) to indicate a number andtype of drug depots contained in the device and/or delivered into apatient. Additionally, expiration date, lot number, trademarks,application information, and classification of drug are optionallyprovided on the housing. The indicia is also optionally provided in theform of color coding of at least portions of the housing. Indicia in thethird and fourth embodiments is optionally provided on the ring membersthereof, but are also optionally provided elsewhere on the housingbodies. For exemplary purposes and without limitation, the ring membersare color coded. In various embodiments, the plunger includes markingsthat indicate location at or near the site beneath the skin.

Plunger

In each of the aforesaid embodiments of the present disclosure theplunger knob 122 optionally has alignment ridges 125 which areconfigured to align the plunger knob 122 with any of the funnel bodies,102, 102 a-102 c, by virtue of engagement with the funnel bore 150 whenthe plunger 120 is fully inserted into the drug delivery device.Additionally, the alignment ridges 125 provide structural support forthe push rod 125.

Although the first end of the plunger is shown as a knob, it will beunderstood that the knob can be a top, dial, cap, handle or any memberthat allows the user to utilize the plunger. The plunger has a secondend that includes a tip, which is capable of moving the drug depotwithin the cannula. In other embodiments, the tip of the plunger issufficiently pointed so that it is capable of insertion to the sitebeneath the skin of the patient and the cannula or needle is blunted andused to guide the drug depot to the site.

The plunger has a diameter less than the cannula or needle so that itcan be slidably received therein. The plunger may be longer, the samesize, or smaller in length than the cannula or needle. In embodimentswhere the plunger extends from the distal end of the cannula or needle,the plunger is usually longer than the cannula or needle. In someembodiments, the tip of the plunger can be sharp or blunt.

The plunger may be made from materials, such as for example,polyurethane, polyurea, polyether(amide), PEBA, thermoplasticelastomeric olefin, copolyester, and styrenic thermoplastic elastomer,steel, aluminum, stainless steel, titanium, nitinol, metal alloys withhigh non-ferrous metal content and a low relative proportion of iron,carbon fiber, glass fiber, plastics, ceramics or combinations thereof.The plunger may optionally include one or more tapered regions.

Like the cannula or needle, in various embodiments, the plunger may havedose indicator markings (e.g., numbers, lines, letters, radiographicmarkers, etc.) to indicate the number of drug depots delivered. Invarious embodiments, the plunger includes markings that indicatelocation at or near the site beneath the skin.

The plunger tip, which may be a complementary shape to the drug pellet,allows the plunger tip to snuggly fit within the end of the drug pelletfor easier drug delivery. The drug pellet may have a rounded end foreasier insertion at the desired site.

Drug Depot Composition and Manufacture

In various embodiments, including those described above, the drugdelivery device optionally comprises at least one drug depot disposedtherein during assembly. Alternatively, the drug delivery device isprovided assembled without a drug therein and at least one drug depot isbreach loaded in to the drug delivery device at a time of use. A furtheralternative is to provide the various components of the drug deliverydevice in a kit which allows loading of a drug depot into the drugcartridge of the respective device at the time of assembly.

A drug depot comprises a physical structure to facilitate implantationand retention in a desired site (e.g., a synovial joint, a disc space, aspinal canal, a tissue of the patient, etc.). The drug depot alsocomprises the drug. The term “drug” as used herein is generally meant torefer to any substance that alters the physiology of the patient. Theterm “drug” may be used interchangeably herein with the terms“therapeutic agent”, “therapeutically effective amount”, and “activepharmaceutical ingredient”. It will be understood that a “drug”formulation may include more than one therapeutic agent, whereinexemplary combinations of therapeutic agents include a combination oftwo or more drugs. The drug provides a concentration gradient of thetherapeutic agent for delivery to the site. In various embodiments, thedrug depot provides an optimal drug concentration gradient of thetherapeutic agent at a distance of up to about 1 mm to about 5 cm fromthe implant site.

Examples of drugs suitable for use in the drug depot, include, but arenot limited to an anti-inflammatory agent, analgesic agent, orosteoinductive growth factor or a combination thereof. Anti-inflammatoryagents include, but are not limited to, salicylates, diflunisal,indomethacin, ibuprofen, naproxen, tolmetin, ketorolac, diclofenac,ketoprofen, fenamates (mefenamic acid, meclofenamic acid), enolic acids(piroxicam, meloxicam), nabumetone, celecoxib, etodolac, nimesulide,apazone, gold, sulindac or tepoxalin; antioxidants, such asdithiocarbamate, and other compounds such assulfasalazine[2-hydroxy-5-[-4-[C2-pyridinylamino)sulfonyl]azo]benzoicacid], steroids, such as fluocinolone, cortisol, cortisone,hydrocortisone, fludrocortisone, prednisone, prednisolone,methylprednisolone, triamcinolone, betamethasone, dexamethasone,beclomethasone, fluticasone or protein inhibitors of TNF, such asetanercept, Remicade, IL-1, such as Kineret®, p38, RANK, RANKL, or acombination thereof.

Suitable osteoinductive factors include, but are not limited to, a bonemorphogenetic protein, a growth differentiation factor, a LIMmineralization protein or a combination thereof.

Suitable analgesic agents include, but are not limited to,acetaminophen, lidocaine, bupivicaine, opioid analgesics such asbuprenorphine, butorphanol, dextromoramide, dezocine,dextropropoxyphene, diamorphine, fentanyl, alfentanil, sufentanil,hydrocodone, hydromorphone, ketobemidone, levomethadyl, mepiridine,methadone, morphine, nalbuphine, opium, oxycodone, papaveretum,pentazocine, pethidine, phenoperidine, piritramide, dextropropoxyphene,remifentanil, tilidine, tramadol, codeine, dihydrocodeine, meptazinol,dezocine, eptazocine, flupirtine or a combination thereof. Analgesicsalso include agents with analgesic properties, such as for example,amitriptyline, carbamazepine, gabapentin, pregabalin, clonidine, or acombination thereof.

A “depot” includes but is not limited to capsules, microspheres,particles, coating, matrices, wafers, pills, pellets or otherpharmaceutical delivery compositions. In various embodiments, the depotmay comprise a bioerodible, a bioabsorbable, and/or a biodegradablebiopolymer that may provide immediate release, or sustained release ofthe drug. Examples of suitable sustained release biopolymers include butare not limited to poly(alpha-hydroxy acids), poly(lactide-co-glycolide)(PLGA), polylactide (PLA), polyglycolide (PG), polyethylene glycol (PEG)conjugates of poly(alpha-hydroxy acids), poly(orthoester)s (POE),polyaspirins, polyphosphagenes, collagen, starch, pre-gelatinizedstarch, hyaluronic acid, chitosans, gelatin, alginates, albumin, fibrin,vitamin E analogs, such as alpha tocopheryl acetate, d-alpha tocopherylsuccinate, D,L-lactide, or L-lactide, -caprolactone, dextrans,vinylpyrrolidone, polyvinyl alcohol (PVA), PVA-g-PLGA, PEGT-PBTcopolymer (polyactive), methacrylates, poly(N-isopropylacrylamide),PEO-PPO-PEO (pluronics), PEO-PPO-PAA copolymers, PLGA-PEO-PLGA, PEG-PLG,PLA-PLGA, poloxamer 407, PEG-PLGA-PEG triblock copolymers, SAIB (sucroseacetate isobutyrate) or combinations thereof. As persons of ordinaryskill are aware, mPEG may be used as a plasticizer for PLGA, but otherpolymers/excipients may be used to achieve the same effect. mPEG impartsmalleability to the resulting formulations. In various embodiments, thedrug depot comprises poly(lactide-co-glycolide) (PLGA), polylactide(PLA), polyglycolide (PGA), D-lactide, D,L-lactide, L-lactide,D,L-lactide-ε-caprolactone, D,L-lactide-glycolide-ε-caprolactone or acombination thereof.

In various embodiments, the drug depot comprises drug pellets, asillustrated in the figures of the above described embodiments, loadedwith a therapeutically effective amount of the therapeutic agent,wherein the pellets are injected into a synovial joint, a disc space, aspinal canal, or a soft tissue surrounding the spinal canal. In variousembodiments, the drug pellets comprise a gel in viscous form andmicrospheres loaded with a therapeutic agent, wherein the combination ofgel and microspheres are positioned into a synovial joint, disc space, aspinal canal, or a soft tissue surrounding the spinal canal of asubject.

A “therapeutically effective amount” is such that when administered, thedrug results in alteration of the biological activity, such as, forexample, inhibition of inflammation, reduction or alleviation of pain,improvement in the condition, etc. The dosage administered to a patientcan be as single or multiple doses depending upon a variety of factors,including the drug's pharmacokinetic properties, the route ofadministration, patient conditions and characteristics (sex, age, bodyweight, health, size, etc.), extent of symptoms, concurrent treatments,frequency of treatment and the effect desired.

In the above described exemplary embodiments, the drug depot is in theform of a pellet. The pellet can be any shape, such as for example,bullet shaped, spherical, substantially spherical, flaked, rod shaped(as presented in the figures), square, oval, etc. In variousembodiments, the drug pellet has an aspect ratio (a ratio of the lengthof the pellet divided by the width found at an angle of 90° in respectto the length) which is less than about 1.4 to about 1.05.

The proximal end of the drug pellet may allow the plunger tip to snugglyfit within the proximal end of the drug pellet for easier drug delivery.The distal end of the drug pellet may be rounded for easier insertion atthe site.

In various embodiments, the drug pellet comprises a bullet-shaped bodythat is made from a biodegradable material. In alternative embodiments,the body of the pellet may be made from a non-biodegradable material. Anon-biodegradable body could be a porous hollow chamber filled with thetherapeutic agent alone or incorporated into a degradable polymer. Itmay be desirable to make the body non-degradable to be able to retrieveit after it has released its contents. Non-limiting examples of suitablebiodegradable materials for the pellet body include polyorthoesters(POE), polylacticglycolic acid (PLGA) polysacharides (Saber technology),polycapralactone, polyfumarate, tyrosine polycarbonate, etc. The bodymay be solid, and the therapeutic agent may be dispersed throughout thematerial that forms the body. The dispersal of the therapeutic agent maybe even throughout the body. Alternatively, the concentration of thetherapeutic agent may vary throughout the body. As the biodegradablematerial of the body degrades at the site, the therapeutic agent isreleased.

Procedures for making pellets include, but are not limited to,extrusion-spheroidization, for spherical pellets where the activepharmaceutical ingredient (API) and any inactive ingredients(excipients, binders, etc.) are pre-mixed, then wetted with water, in ahigh shear mixer to form a damp mass. The damp mass is then transferredinto an extruder where it is forced through a screen or die plate, whereit forms an essentially solid, cylindrical extrudate of uniform shapeand size. The size of the opening in the screen or die dictate resultantpellet size. The extrudate is fed onto a rotating disk, which may besmooth or may contain a grid (waffled, grooved, etc.) and the extrudatebreaks into small cylinders, which in time are rounded into sphericallyshaped solids. Subsequently, the pellets are dried to the desiredresidual moisture content, typically in a fluid bed dryer. Any oversizedor undersized product is removed by sieving, and the resulting pelletshave a narrow size distribution.

In various embodiments, the API is layered on the solid core of thepellet by solution or suspension layering or powder layering techniques.In solution or suspension layering, an API and any inactive ingredients(excipients, binders, etc.) are suspended or dissolved in water or anorganic solvent. The resulting liquid is sprayed onto the outside of acore particle, which may include, for example, non-pareil sugar seed(sugar sphere), microcrystalline cellulose pellets and the like, to makethe pellet having the desired potency. Solution or suspension layeringmay be conducted using a wide variety of process techniques, forexample, by fluidized bed, Wurster bottom spray techniques, or the like.When the desired potency has been achieved, pellets are dried to thedesired residual moisture content. Any oversized or undersized productmay be removed by sieving, and the resulting pellets are narrow in sizedistribution.

Powder layering may also be used to make the drug pellets. Powderedlayering involves the application of a dry powder to the pellet corematerial. The powder may contain the drug, or may include excipientssuch as a binder, flow aid, inert filler, and the like. In the powderlayering technique a pharmaceutically acceptable liquid, which may bewater, organic solvent, with or without a binder and/or excipients, isapplied to the core material while applying the dry powder until thedesired potency is achieved. When the desired potency has been achieved,the pellets may be seal coated to improve their strength, and are thendried to the desired moisture content. Any oversized or undersizedproduct is removed by sieving, and the resulting pellets are narrow insize distribution.

In one embodiment, the pellet is made using a core of biodegradablematerial, such as, for example, polyglactin, polylactone, polylactide,etc. The core is then coated with a thin layer of the API, such as ananti-inflammatory agent, analgesic agent, etc. by solution, suspension,or powdered layering until the desired potency is achieved.

In various embodiments, the drug pellets can be different sizes, forexample, from about 1 mm to 5 mm in length and have a diameter of fromabout 0.01 to about 2 mm. The layer or layers will each have a layerthickness of from about 0.005 to 1.0 mm, such as, for example, from 0.05to 0.75 mm.

Like the cannula, needle, or plunger, in various embodiments, the drugdepot (e.g., pellet, cartridge, etc.) may have dose indicator markings(e.g., numbers, lines, letters, radiographic markers, etc.) to indicatethe number of drug depots delivered. In various embodiments, radiopaquemarks are positioned on the depot at opposite ends of the depot toassist in determining the position of the depot relative to thetreatment site. For example, the radiopaque marker could be a sphericalshape or a ring around the depot.

Drug Cartridge Material, Loading and Sterilization

In various embodiments, including those presented above, the drugcartridge may be made from materials, such as for example, polyurethane,polyurea, polyether(amide), PEBA, thermoplastic elastomeric olefin,copolyester, and styrenic thermoplastic elastomer, steel, aluminum,stainless steel, titanium, nitinol, metal alloys with high non-ferrousmetal content and a low relative proportion of iron, carbon fiber, glassfiber, plastics, ceramics or a combination thereof. In variousembodiments, the drug cartridge is not biodegradable.

The drug device components (e.g., cannula or needle, plunger, housing,funnel body, etc.) are optionally lightweight, disposable andsterilizable such that when the device is assembled (e.g., the drugcartridge is loaded the housing), the weight of the device does notsubstantially increase. In various embodiments, one or more componentsof the device are sterilized by radiation in a terminal sterilizationstep in the final packaging. Terminal sterilization of a productprovides greater assurance of sterility than from processes such as anaseptic process, which require individual product components to besterilized separately and the final package assembled in a sterileenvironment.

Typically, in various embodiments, gamma radiation is used in theterminal sterilization step, which involves utilizing ionizing energyfrom gamma rays that penetrates deeply in the device. Gamma rays arehighly effective in killing microorganisms, they leave no residues norhave sufficient energy to impart radioactivity to the device. Gamma rayscan be employed when the device is in the package and gammasterilization does not require high pressures or vacuum conditions,thus, package seals and other components are not stressed. In addition,gamma radiation eliminates the need for permeable packaging materials.

In various embodiments, the drug cartridge provides the advantages ofease of manufacturing in the terminal sterilization process. If the drugpellets are preloaded in the manufacturing process, gamma radiation maybe required at higher doses to sterilize the drug depot loaded in thecannula or needle. This is particularly so when the cannula or needle ismade from steel or metal. Thus, to sterilize the loaded depot, the doseof gamma rays must be high enough to penetrate the metal, which maydestroy the API in the drug depot. By providing a drug cartridge, forexample, made of plastic, the drug cartridge and drug pellets in thecartridge can be sterilized, without destroying the API and thensubsequently loaded by the manufacturer or the user (e.g., surgeon,physician, nurse, etc.). Further, loading the drug depot into the drugchamber or cannula is easier. This is particularly so when dealing withmulti-dose drug pellets that are relatively small (e.g., 1 mm to 5 mm),the user typically cannot grasp these small pellets and load them intothe device. By providing them in a drug cartridge, the user does nothave to substantially manipulate the individual drug pellets and therisk of contaminating the pellets particularly with sterilized pelletsis reduced.

In various embodiments, electron beam (e-beam) radiation may be used tosterilize one or more components of the device. E-beam radiationcomprises a form of ionizing energy, which is generally characterized bylow penetration and high-dose rates. E-beam irradiation is similar togamma processing in that it alters various chemical and molecular bondson contact, including the reproductive cells of microorganisms. Beamsproduced for e-beam sterilization are concentrated, highly-chargedstreams of electrons generated by the acceleration and conversion ofelectricity. E-beam sterilization may be used, for example, when thedrug depot includes a gelatin capsule.

Other methods may also be used to sterilize one or more components ofthe device, including, but not limited to, gas sterilization, such as,for example, with ethylene oxide or steam sterilization.

In some embodiments, the housing, drug cartridge, and/or cannula aretransparent so the user can see the position of the plunger and/or thedrug depot in the chamber of the drug cartridge. Thus, indicatormarkings, in this embodiment, are not needed.

Drug Delivery Device Kit

In various embodiments, a kit is provided which may include additionalparts along with the drug delivery device combined together to be usedto implant the drug depot. The kit may include the drug delivery devicein a first compartment. The second compartment may include the drugcartridge, and any other instruments needed for the implant. A thirdcompartment may include gloves, drapes, wound dressings and otherprocedural supplies for maintaining sterility of the implanting process,as well as an instruction booklet. A fourth compartment may includeadditional cannulas and/or needles. Each tool may be separately packagedin a plastic pouch that is radiation sterilized. A cover of the kit mayinclude illustrations of the implanting procedure and a clear plasticcover may be placed over the compartments to maintain sterility.

Method of Using the Drug Delivery Device.

In various embodiments of the present disclosure, a method is providedfor delivering a drug depot to a site beneath the skin of a patient, themethod comprising: assembling a drug delivery device wherein the drugdelivery device comprises a cannula having a proximal end and a distalend, the proximal end of the cannula having an opening to receive thedrug depot, the distal end of the cannula capable of insertion to thesite beneath the skin of the patient and having an opening for passageof the drug depot; a cartridge comprising components to form a securechamber wherein the secure chamber is capable of storing one or moredrug depots in the form of drug pellets, a housing having a top end, abottom end, and an interior cavity wherein the bottom end of the housinghas a coupling means for coupling to the proximal end of the cannula andwherein the interior cavity is configured to receive the cartridge; aplunger having a knob end and a tip end for expelling a drug pellet fromthe secure chamber, wherein the tip end is slidably receivable withineach of the housing, the cartridge, and the cannula to deliver the drugpellet to the site beneath the skin of the patient; selecting a drugdelivery site beneath the skin of the patient; and dispensing the drugpellet from the drug delivery device to a site beneath the skin of thepatient.

In various embodiments, the seal between the plunger tip and the cannulaor needle can be air tight so that when the cannula or plungerpenetrates the skin, at times, fluid (e.g., blood, spinal fluid,synovial fluid, etc.) may be drawn up into the cannula or needle. Thisfluid will be expelled when the plunger is re-inserted into the cannulaor needle and the drug depot is released.

The device may be used for localized and/or targeted delivery of thedrug to a patient to treat a disease or condition such as for example,rheumatoid arthritis, osteoarthritis, sciatica, carpal tunnel syndrome,lower back pain, lower extremity pain, upper extremity pain, cancer,tissue pain and pain associated with injury or repair of cervical,thoracic, and/or lumbar vertebrae or intervertebral discs, rotator cuff,articular joint, TMJ, tendons, ligaments, bone, muscles, and the like.

In various embodiments, the drug delivery device is used to treat pain,or other diseases or conditions of the patient. Pain includes acute painand neuropathic pain. Acute pain refers to pain experienced when tissueis being damaged or is damaged (e.g., injury, infection, etc.). Ascontrasted to acute pain, neuropathic pain serves no beneficial purpose.Neuropathic pain results when pain associated with an injury orinfection continues in an area once the injury or infection hasresolved. Sciatica provides an example of pain that can transition fromacute to neuropathic pain. Sciatica refers to pain associated with thesciatic nerve which runs from the lower part of the spinal cord (thelumbar region), down the back of the leg and to the foot. Sciaticagenerally begins with a herniated disc. The herniated disc itself leadsto local immune system activation. The herniated disc also may damagethe nerve root by pinching or compressing it, leading to additionalimmune system activation in the area.

DEFINITIONS

Patients include a biological system to which a treatment can beadministered. A biological system can include, for example, anindividual cell, a set of cells (e.g., a cell culture), an organ, or atissue. Additionally, the term “patient” can refer to animals,including, without limitation, humans.

Treating or treatment of a disease refers to executing a protocol, whichmay include administering one or more drugs to a patient (human orotherwise), in an effort to alleviate signs or symptoms of the disease.Alleviation can occur prior to signs or symptoms of the diseaseappearing, as well as after their appearance. Thus, “treating” or“treatment” includes “preventing” or “prevention” of disease. Inaddition, “treating” or “treatment” does not require completealleviation of signs or symptoms, does not require a cure, andspecifically includes protocols that have only a marginal effect on thepatient.

“Localized” delivery includes, delivery where one or more drugs aredeposited within a tissue, for example, a nerve root of the nervoussystem or a region of the brain, or in close proximity (within about 10cm, or preferably within about 5 cm, for example) thereto. “Targeteddelivery system” provides delivery of one or more drugs depots in aquantity of pharmaceutical composition that can be deposited at thetarget site as needed for treatment of pain, inflammation or otherdisease or condition.

It will be apparent to those skilled in the art that variousmodifications and variations can be made to various embodimentsdescribed herein without departing from the spirit or scope of theteachings herein. Thus, it is intended that various embodiments coverother modifications and variations of various embodiments within thescope of the present teachings.

What is claimed is:
 1. A device for delivering a drug depot to a sitebeneath the skin of patient via a cannula having a proximal end and adistal end, the proximal end of the cannula having an opening to receivethe drug depot, the distal end of the cannula being configured forinsertion to the site beneath the skin of the patient and having anopening for passage of the drug depot, the device comprising: a housingincluding a lower body, an upper body, a ring member; and a drugcartridge, said housing having a housing upper end, a housing lower endand a longitudinal direction defined as extending from said housingupper end to said housing lower end; said lower body having a lower bodybottom end, a lower body upper end, and an annular step surfaceextending inward from an outer periphery of said lower body, and saidlower body defining a lower body channel extending in said longitudinaldirection; said lower body channel having a lower body channel first endopen to said lower body upper end and a lower body channel second endopen to said lower body bottom end; said lower body bottom end having acoupling configuration for engaging the proximal end of the cannula;said upper body having an upper body top end and an upper body bottomend, said upper body defining an upper body channel open to said upperbody top end, and said upper body being connected to said lower body;said drug cartridge defining a depot channel aligned with said lowerbody channel and said upper body channel, and configured to slidablyaccept the drug depot; said ring member having a ring top end and a ringbottom end, and said ring member being disposed so as to extend upwardfrom said annular step surface toward said housing upper end and so asto contact at least one of said upper body and said lower body; and aplunger having a push rod slidably receivable in said upper bodychannel, said depot channel, said lower body channel, and the cannulaand having a push rod end to contact the drug depot when disposed insaid drug cartridge and, upon application of force, expel the drug depotthrough the cannula to the site beneath the skin of the patient.
 2. Adevice for delivering a drug depot according to claim 1, wherein: saidring member has a ring upper surface extending at least partially in aradially inward direction of said ring member; and said upper body hasan upper body surface extending at least partially in the radiallyoutward direction of said ring member so as to increase a width of saidupper with approach to said upper body end, and said upper body surfaceengaging said ring upper surface so as to inhibit movement of said ringmember in an upward direction.
 3. A device for delivering a drug depotaccording to claim 2, wherein said ring member extends from said annularstep surface to said housing upper end so as to surround said housingupper end.
 4. A device for delivering a drug depot according to claim 3,wherein said ring upper surface is inclined with respect to a ringcenter axis of said ring member, and said upper body surface is inclinedwith respect to said ring center axis.
 5. A device for delivering a drugdepot according to claim 4, wherein: said upper body is connected tosaid lower body by contacting engagement with said lower body; and saidring member is secured in the longitudinal direction between saidannular step surface of said lower body and said upper body surface ofsaid upper body.
 6. A device for delivering a drug depot according toclaim 5, wherein said contacting engagement is effected by a cantileverarm snap catch configuration incorporated into said upper body and saidlower body.
 7. A device for delivering a drug depot according to claim6, wherein said upper body channel has a funnel configuration extendingand narrowing in a direction from said upper body top end to said upperbody bottom end.
 8. A device for delivering a drug depot according toclaim 6, wherein said device includes the drug depot being disposed insaid drug cartridge, and said ring member has an outer surface which isat least one of color coded indicating a characteristic of said drugdepot or marked with indicia indicating a characteristic of said drugdepot.
 9. A device for delivering a drug depot according to claim 2,wherein: said ring member extends from said annular step surface andends at a position below said housing upper end; said upper body has aperipheral ring extending radially outward and above said ring member,said peripheral ring having said upper body surface as a bottom surface;and said peripheral ring having an outer peripheral surface disposedabove said ring member.
 10. A device for delivering a drug depotaccording to claim 3, wherein said ring upper surface and said upperbody surface are substantially perpendicular to said longitudinal axis.11. A device for delivering a drug depot according to claim 10, wherein:said upper body is connected to said lower body by contacting engagementwith said lower body; and said ring member is secured in thelongitudinal direction between said annular step surface of said lowerbody and said upper body surface of said upper body.
 12. A device fordelivering a drug depot according to claim 11, wherein said contactingengagement is effected by a cantilever arm snap catch configurationincorporated into said upper body and said lower body.
 13. A device fordelivering a drug depot according to claim 12, wherein said upper bodychannel has a funnel configuration extending and narrowing in adirection from said upper body top end to said upper body bottom end.14. A device for delivering a drug depot according to claim 13, wherein:said housing has a viewing configuration disposed to permit viewing of adrug depot disposed in said drug cartridge; and said drug cartridge isformed of a material permitting viewing of a drug depot held within saiddrug cartridge.
 15. A device for delivering a drug depot according toclaim 6, wherein said device includes the drug depot being disposed insaid drug cartridge, and said ring member has an outer surface withindicia in the form of at least one of color coded indicating acharacteristic of said drug depot or text indicating a characteristic ofsaid drug depot.
 16. A kit for preparing a device for delivering a drugdepot to a site beneath the skin of a patient in conjunction with acannula having a proximal end and a distal end, the proximal end of thecannula having an opening to receive the drug depot, the distal end ofthe cannula being configured for insertion to the site beneath the skinof the patient and having an opening for passage of the drug depot, thekit comprising: components for a housing including a lower body, anupper body, a ring member; and a drug cartridge, said housing whenassembled having a housing upper end, a housing lower end and alongitudinal direction defined as extending from said housing upper endto said housing lower end; said lower body having a lower body bottomend, a lower body upper end, and an annular step surface extendinginward from an outer periphery of said lower body, and said lower bodydefining a lower body channel extending in said longitudinal direction;said lower body channel having a lower body channel first end open tosaid lower body upper end and a lower body channel second end open tosaid lower body bottom end; said lower body bottom end having a couplingconfiguration for engaging the proximal end of the cannula; said upperbody having an upper body top end and an upper body bottom end, saidupper body defining an upper body channel open to said upper body topend, and said upper body being connectable by snap catches to said lowerbody; said drug cartridge defining a depot channel alignable with saidlower body channel and said upper body channel when installed in saidlower body, and said depot channel being configured to slidably acceptthe drug depot; said ring member having a ring top end and a ring bottomend, and said ring member being disposable so as to extend upward fromsaid annular step surface toward said housing upper end and so as tocontact at least one of said upper body and said lower body whenassembled with said upper body and said lower body; and a plunger havinga push rod slidably receivable in said upper body channel, said depotchannel, said lower body channel, and the cannula and having a push rodend to contact the drug depot when disposed in said drug cartridge and,upon application of force, expel the drug depot through the cannula tothe site beneath the skin of the patient.
 17. A kit for delivering adrug depot according to claim 16, further comprising: drug depots; saidring member including at least two ring members having indicia embodiedas at least one of color coding or text corresponding to characteristicsof said drug depots or a combination of said drug depots.
 18. A methodfor preparing a device for delivering a drug depot to a site beneath theskin of a patient in conjunction with a cannula having a proximal endand a distal end, the proximal end of the cannula having an opening toreceive the drug depot, the distal end of the cannula being configuredfor insertion to the site beneath the skin of the patient and having anopening for passage of the drug depot, the method comprising: providinga kit according to claim 17; selecting one or more of said drug depots;selecting one of said at least two rings members having indiciacorresponding to said selected one or more of said drug depots; slidingsaid selected one of said at least two ring members onto one of saidupper body or said lower body; installing said upper body and said drugcartridge to said lower body including engaging said upper body to saidlower body using said snap catches; loading said drug cartridge withsaid selected one or more drug depots; and engaging said cannula withsaid lower body.
 19. A method of claim 18, further comprising: said drugcartridge comprising a first plate and a second plate; and said loadingsaid drug cartridge including placing said selected one or more drugdepots into a portion of said depot channel and assembling said firstplate to said second plate prior to said installing said upper body andsaid drug cartridge to said lower body.
 20. A method of claim 18,wherein said loading said drug cartridge includes breach loading saiddrug cartridge comprising: inserting said selected one or more drugdepots into said upper body channel after said installing said upperbody and said drug cartridge to said lower body; and inserting said pushrod into said upper body channel to a position whereat said selected oneor more drug depots are pushed into said drug cartridge by said pushrod.